Cytochrome bd as survival factor in mycobacteria

Ping Lu, Marieke Heineke, Anil Koul, Koen Andries, Gregory M. Cook, Holger Lill, Rob van Spanning, Dirk Bald

Research output: Contribution to JournalArticleAcademicpeer-review


Targeting respiration and ATP synthesis has received strong interest as a new strategy for combating drug-resistant Mycobacterium tuberculosis [1,2]. Mycobacteria employ a respiratory chain terminating with two branches. One of the branches includes a cytochrome bc1 complex and an aa3-type cytochrome c oxidase while the other branch terminates with a cytochrome bd-type quinol oxidase. We have shown that genetic inactivation of cytochrome bd, but not of cytochrome bc1, enhances the susceptibility of Mycobacterium smegmatis to hydrogen peroxide and antibiotic-induced stress [3]. The type-II NADH dehydrogenase effector clofazimine and the ATP synthase inhibitor bedaquiline were bacteriostatic against wild-type M. smegmatis, but strongly bactericidal against a cytochrome bd knock-out mutant [3,4]. These results identify cytochrome bd as a key survival factor in mycobacteria. The quinone-analog aurachin D inhibited mycobacterial cytochrome bd at sub-micromolar concentrations. Progress towards the characterization of cytochrome bd and its inhibitors will be discussed. Targeting the cytochrome bd respiratory branch appears to be a promising strategy that may enhance the bactericidal activity of existing tuberculosis drugs.
Original languageEnglish
Pages (from-to)e120
JournalBiochimica et Biophysica Acta (BBA) - Bioenergetics
Publication statusPublished - Aug 2016


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